Psychotic Experiences and Neuropsychological Functioning

Research
Original Investigation
Psychotic Experiences and Neuropsychological Functioning
in a Population-based Sample
Josephine Mollon, MSc; Anthony S. David, MD, FRCPsych; Craig Morgan, MSc, PhD; Souci Frissa, PhD; David Glahn, PhD;
Izabela Pilecka, BSc; Stephani L. Hatch, PhD; Matthew Hotopf, MRCPsych, PhD; Abraham Reichenberg, PhD
Editorial page 109
IMPORTANCE Psychotic experiences in early life are associated with neuropsychological
impairment and the risk for later psychiatric disorders. Psychotic experiences are also
prevalent in adults, but neuropsychological investigations spanning adulthood are limited,
and confounding factors have not been examined rigorously.
Supplemental content at
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OBJECTIVE To characterize neuropsychological functioning in adults with psychotic
experiences while adjusting for important sociodemographic characteristics and familial
factors and investigating the effect of age.
DESIGN, SETTING, AND PARTICIPANTS The South East London Community Health (SELCoH)
study is a population-based household survey of physical and mental health in individuals 16
years or older conducted from June 1, 2008, to December 31, 2010, in 2 London boroughs.
The study included 1698 participants from 1075 households. Data were analyzed from May 6,
2014, to April 22, 2015.
EXPOSURES Psychotic experiences measured using the Psychosis Screening Questionnaire.
MAIN OUTCOMES AND MEASURES Neuropsychological functioning measured using tests
assessing verbal knowledge (Wechsler Test of Adult Reading), working memory (Spatial
Delayed Response Task), memory (Visual Object Learning Task), and processing speed (digit
symbol coding task). A composite IQ score of general cognitive ability was calculated.
RESULTS A total of 1677 participants with a mean (SD) age of 40 (17) years were included in
the analysis. Compared with the group without psychotic experiences, the 171 (9.7%) adults
with psychotic experiences did not show a statistically significant impairment on mean (SD)
measures of IQ (95.25 [16.58] vs 100.45 [14.77]; Cohen d, −0.22; P = .06) or processing speed
(40.63 [13.06] vs 42.17 [13.79]; Cohen d, −0.03; P = .73) but were impaired on measures of
verbal knowledge (31.36 [15.78] vs 38.83 [12.64]; Cohen d, −0.37; P = .003), working memory
(20.97 [4.12] vs 22.51 [3.26]; Cohen d, −0.34; P = .005), and memory (43.80 [8.45] vs 46.53
[7.06]; Cohen d, −0.28; P = .01). Only participants 50 years and older with psychotic
experiences showed medium to large impairments in neuropsychological functioning (mean
[SD]) on measures of IQ (81.22 [15.97] vs 91.28 [14.31]; Cohen d, −0.70), verbal knowledge
(28.31 [13.83] vs 38.51 [11.50]; Cohen d, −0.88), working memory (19.11 [4.77] vs 21.99 [3.42];
Cohen d, −0.82), and memory (39.17 [8.23] vs 44.09 [6.51]; Cohen d, −0.45) after adjusting for
socioeconomic status, cannabis use, and common mental disorders. Medium impairments
(mean [SD]) on measures of working memory (21.27 [3.64] vs 22.62 [2.97]; Cohen d, −0.45)
and memory (44.32 [5.84] vs 46.91 [5.74]; Cohen d, −0.45) were seen in those aged 35 to 49
years and on a measure of verbal knowledge (30.81 [14.17] vs 37.60 [10.48]; Cohen d, −0.62) in
those aged 16 to 24 years. First-degree relatives of adults with psychotic experiences showed a
small impairment on a measure of verbal knowledge (34.71 [12.10] vs 38.63 [10.97]; Cohen d,
−0.36; P = .02), and unrelated cohabitants showed no neuropsychological impairment.
CONCLUSIONS AND RELEVANCE The profile of cognitive impairment in adults with psychotic
experiences differed from that seen in adults with psychotic disorders, suggesting important
differences between subclinical and clinical psychosis.
JAMA Psychiatry. 2016;73(2):129-138. doi:10.1001/jamapsychiatry.2015.2551
Published online December 30, 2015.
Author Affiliations: Author
affiliations are listed at the end of this
article.
Corresponding Author: Josephine
Mollon, MSc, Department of
Psychosis Studies, Institute of
Psychiatry, Psychology, and
Neuroscience, King’s College London,
London SE5 8AF, England
([email protected]).
(Reprinted) 129
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Research Original Investigation
Psychotic Experiences and Neuropsychological Functioning
S
chizophrenia has a lifetime prevalence of approximately 1% and combined psychotic disorders of approximately 3%.1,2 A substantial minority of the general population also reports subclinical psychotic experiences, with the
World Health Organization World Mental Health Surveys3 reporting a lifetime prevalence of 5.8% worldwide and of 6.8%,
7.2%, and 3.2% in high-, middle-, and low-income countries,
respectively. Evidence suggests that subclinical psychotic experiences may lie on a continuum with clinically significant
psychotic symptoms and therefore be informative for research into the cause of psychotic illness. First, psychotic experiences and psychotic disorders share risk factors, including low IQ, childhood maltreatment, and stressful life events.4,5
Second, imaging studies report pathophysiologic overlaps between subclinical and clinical psychosis, including hypofrontality, frontotemporal disconnection, and deficits in gray and
white matter.6-8 Finally, psychotic experiences in early life are
associated with an increased risk for later psychotic illness9,10
and in adulthood with later hospitalization for a psychotic
disorder.11 However, psychotic experiences are also associated with nonpsychotic psychiatric disorders, including anxiety, depression,12,13 and suicidal thoughts and behavior.14,15
Lending support to this hypothesized psychosis continuum are the small neuropsychological impairments seen in
people with psychotic experiences. (Table 1 and eMethods
and eFigure 1 in the Supplement report results of a metaanalysis of previous population studies of neuropsychological
functioning and psychotic experiences).4,5,16-40 Neuropsychological impairment is a core feature of schizophrenia41,42; it
emerges early and remains relatively stable throughout the
course of the illness.43 The most severe impairment is reported in processing speed, 44,45 but deficits in episodic
memory and working memory have been proposed as core
features.46 A similar profile of impairment has been reported
in people with psychotic experiences,19,20 but most of the
studies have focused on child and adolescent samples,
despite evidence that psychotic experiences are prevalent
across the life course.3,5,47,48 Only 1 study in our meta-analysis
investigated the neuropsychological correlates of psychotic
experiences across adulthood5 and reported on a single cognitive domain. Moreover, previous studies have not adjusted for
key sociodemographic confounders, whose importance is
highlighted by the World Mental Health Surveys’ finding of
higher prevalences of psychotic experiences in middle- and
high-income countries compared w ith low-income
countries.3 Finally, the association between psychotic experiences and neuropsychological functioning may be confounded by shared familial factors.49
In the present study we examined subclinical psychotic experiences and neuropsychological functioning in adults from
an ethnically and sociodemographically diverse population.
Our study was unique in examining the effects of (1) important confounders, including cannabis use and psychiatric morbidity, (2) age, and (3) confounding by familial factors on the
association between psychotic experiences and neuropsychological functioning. We hypothesized that psychotic experiences would be associated with a profile of cognitive impairment similar, yet milder, to that of schizophrenia, characterized
130
by specific deficits in processing speed and memory seen in
the context of a generalized deficit.
Methods
Sample
The South East London Community Health (SELCoH) study is
a population-based household survey completed in 2010 in the
London boroughs of Lambeth and Southwark. The aim was to
provide prevalence estimates of mental and physical health
symptoms in an ethnically and socioeconomically diverse, geographically defined, inner-city community. A random sample
of households was identified using the Small User Postcode Address File (http://www.poweredbypaf.com/), which has nearly
complete coverage of private households in the United Kingdom. Introductory letters were sent to households, which were
visited up to 4 times at different times of the day and the week.
When contact was made, written informed consent was sought
from as many eligible (aged ≥16 years) members of the household as possible; all study participants provided written informed consent. Contact was established with 2070 private
households, of which 1075 had at least 1 member interviewed, representing a 51.9% household participation rate. Of
2359 individuals eligible within the participating households, 1698 (72.0%) participated (a detailed description can
be found in Hatch et al50). This study was approved by the research ethics committee of King’s College London.
Procedure
Data were collected using a computer-assisted interview schedule, which was piloted to establish reliability, validity, and feasibility. Data were collected from June 1, 2008, to December
31, 2010. Participants received £15 for participation.
Measures
Psychotic Experiences
The Psychosis Screening Questionnaire (PSQ)51 was used to
measure psychotic experiences. The PSQ is an intervieweradministered questionnaire that assesses psychotic experiences in the preceding year and consists of 5 sections covering
hypomania, thought disorder, paranoia, strange experiences,
and hallucinations. Items on hypomania were discarded because the focus was on psychosis. Each section has an initial
probe, followed by secondary question(s), which establish the
quality of psychotic experiences. The PSQ has been validated
in 2 national surveys in the United Kingdom.52,53 In this study,
those participants who endorsed 1 or more secondary questions at the highest level on the PSQ were compared with those
who did not5 (eTable 1 in the Supplement).
Neuropsychological Functioning
Verbal knowledge was assessed using the Wechsler Test of
Adult Reading (WTAR),54 working memory with the Spatial Delayed Response Task (SDRT),55 visual memory with the Visual Object Learning Task (VOLT),56 and processing speed with
a digit symbol coding task (DSCT)57,58 (eTable 2 in the Supplement). Neuropsychological tests were administered using a
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Psychotic Experiences and Neuropsychological Functioning
Original Investigation Research
Table 1. Studies Investigating Neuropsychological Functioning and Psychotic Experiences
Domain by Source
No. of
Participants
Age at Measurement
of Cognition, y
Age at Measurement
of Psychotic Experiences, y
Rate of Psychotic
Experiences, %
Effect Size,
Cohen d
IQa
Polanczyk et al,4 2010
2127
Kremen et al,16 1998
547
Horwood et al,17 2008
6384
Cannon et al,18 2002
Pooled effect size
789
NA
5
12
5.9
−0.51
23
3.2
−0.61
8
12
13.8
−0.08
3-11
11
14.7
−0.52
NA
NA
−0.40
4 and 7
NA
General cognitionb
Niarchou et al,19 2013
6784
Kelleher et al,20 2012
165
Barnett et al,21 2012
2916
Gur et al,22 2014
4275
8-21
8-21
15.5
−0.42
Johns et al,5 2004
8520
16-74
16-74
5.5
−0.34
Pooled effect size
NA
NA
NA
8, 10, and 11
12
11.6
−0.05
11-13
11-13
25.5
−0.03
8, 11, and 15
53
22.3
−0.16
NA
−0.19
Processing speedc
Niarchou et al,19 2013
6784
Kelleher et al,20 2012
165
Gur et al,22 2014
Henderson et al,23 1998
Ostling et al,24 2004
Pooled effect size
4275
8, 10, and 11
12
11.6
−0.13
11-13
11-13
25.5
−0.30
8-21
15.5
−0.29
870
78
78
7.5
−0.24
245
85
85
14.3
−0.56
NA
NA
NA
−0.20
NA
8-21
Working memoryd
Niarchou et al,19 2013
6784
Kelleher et al,20 2012
165
Gur et al,22 2014
Ostling et al,24 2004
Pooled effect size
4275
8, 10, and 11
12
11.6
−0.07
11-13
11-13
25.5
−0.09
15.5
−0.29
85
85
14.3
−0.33
NA
NA
NA
−0.18
165
11-13
11-13
25.5
−0.18
4275
8-21
8-21
15.5
−0.32
14.3
−0.29
245
NA
8-21
8-21
Memorye
Kelleher et al,20 2012
Gur et al,22 2014
Ostling et al,24 2004
Pooled effect size
245
NA
85
85
NA
NA
b
IQ measures include Vocabulary and Block Design subtests of Wechsler
Preschool and Primary Scale of Intelligence–Revised29 for Polanczyk et al4;
Stanford-Binet Intelligence Scale (age 4 years)26 and Information, Vocabulary,
Digit Span, Comprehension, Block Design, Picture Arrangement, and Coding
subscales of Wechsler Intelligence Scale for Children (WISC) (age 7 years)30 for
Kremen et al16; WISC III28 for Horwood et al17; and Peabody Picture
Vocabulary Test (age 3 years),25 Stanford-Binet Intelligence Scale (age 5
years),26 and WISC (ages 7, 9, and 11 years)27 for Cannon et al.18
General cognition measures include Picture Completion, Picture Arrangement,
Block Design, and Object Assembly subtests of WISC III28 for Niarchou et
al19;Wide Range Achievement Test 431 for Kelleher et al20; Picture Intelligence,
Reading, Sentence Completion, and Vocabulary (age 8 years), Arithmetic,
Reading, Vocabulary, Verbal, and Nonverbal IQ (age 11 years), and Maths,
Reading, Verbal, and Nonverbal IQ (age 15 years) from AH4 Group Test of
Intelligence33 for Barnett et al21; the Verbal Reasoning, Nonverbal Reasoning,
and Spatial Processing subtests of the Computerized Neurocognitive
computer as in previous schizophrenia and bipolar disorder
studies in which impairments of expected effect sizes were
shown.59-63 We calculated a general cognitive ability composite score as the first principal component of a factor analysis
using all the neuropsychological tests administered.64 Scores
were transformed to an IQ-like score with mean of 100 and SD
of 15.
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22
−0.31
34
Battery (CNB) for Gur et al ; and National Adult Reading Test
et al.5
Abbreviation: NA, not applicable.
a
NA
32
for Johns
c
Processing speed measures include Sky Search Task from Tests for Everyday
Attention for Children36 and the Coding subtest of WISC III28 for Niarchou et
al19; Symbol Coding and Category Fluency in Trail Making Test from MATRICS
neurocognitive battery35 for Kelleher et al20; Symbol Letter Modalities Test37
for Henderson et al23; and Identical Forms Test38 for Ostling et al.24
d
Working memory measures include Backward Digit Span and Arithmetic from
WISC III28 for Niarchou et al19; Spatial Span and Letter Number Span of
Wechsler Memory Scale from MATRICS neurocognitive battery35 for Kelleher
et al20;Abstraction and Mental Flexibility and Attention and Working Memory
subtests of CNB32 for Gur et al22; and Digit Span for Ostling et al.24
e
Memory measures include Hopkins Verbal Learning Test from MATRICS
neurocognitive battery35 for Kelleher et al20;Words, Faces, and Shapes subtests
of CNB32 for Gur et al22; and Thurstone Picture Memory Test38 and Memory in
Reality, Prose Recall, and Ten Word Memory Test40 for Ostling et al.24
Confounders
The interview established ethnicity, age, and occupation classified according to the Registrar General65 as professional (I),
managerial/technical (II), skilled nonmanual (III-NM), skilled
manual (III-M), semiskilled (IV), unskilled (V), and unclassified. Common mental disorders were assessed using the Revised Clinical Interview Schedule (CIS-R),66 which asks about
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Research Original Investigation
Psychotic Experiences and Neuropsychological Functioning
the following 14 symptom domains during the previous week:
fatigue, sleep problems, irritability, worry, depression, depressive ideas, anxiety, obsessions, subjective memory and concentration, somatic symptoms, compulsions, phobias, physical health worries, and panic. A score of 18 or more indicates
the presence of a common mental disorder. Good reliability and
validity of the Revised Clinical Interview Schedule have been
reported. 66,67 Cannabis use in the past year was also reported. Ethnicity, occupation, cannabis use, and common mental disorders were correlated significantly with psychotic experiences and neuropsychological functioning, but minimally
correlated with one another (eTable 3 in the Supplement). Interactions of group (participants with psychotic experiences
or control participants) by confounder (ethnicity, occupation, cannabis use, and common mental disorders) with centered variables68 on all tests were not statistically significant
except for the group by ethnicity interaction on IQ (P = .03).
cal regression curves and to ensure sufficient power. Owing to
the exploratory nature of the age-stratified analyses, Cohen d
effect sizes with associated 95% CIs only are presented herein.
Confounding by familial factors was first examined by plotting local regression curves for age on the interaction of cognition by group (controls, participants with psychotic experiences, first-degree relatives, and unrelated cohabitants) for
each test and subsequently using linear regression, as described above, across the whole sample to ensure sufficient
power. We conducted sensitivity analysis using a different cutoff for the presence of psychotic experiences (ie, yes to ≥1 secondary question at any level70,71) using linear regression, as described above.
Results
Psychotic Experiences
Familial Factors
We investigated familial factors by dividing the cohabitants of
participants with psychotic experiences into 2 groups. The first
group included first-degree relatives (eg, biological child, biological sibling); the second, nongenetically related cohabitants (eg, spouse, nonbiological child).
Data Analysis
Data were analyzed from May 6, 2014, to April 22, 2015. Analyses were completed in STATA software (version 13; StataCorp). Appropriate survey commands (svy) were used to generate robust SEs. All analyses of SELCoH data accounted for
clustering by household inherent in the study design and were
weighted for within-household nonresponse.50
We used linear regression (adjusting for ethnicity, occupational class, cannabis use in the past year, and common mental disorders) to test the hypothesis that psychotic experiences would be associated with impairment in general cognitive
ability (IQ). Because the profile of cognitive impairment in
schizophrenia is characterized by specific deficits in processing speed and memory in the context of a generalized deficit
and because different neural systems underlie performance on
different neuropsychological tests, secondary analyses examined the association between psychotic experiences and individual neuropsychological test results. We applied a Bonferroni correction to adjust for multiple comparisons in the
secondary analyses, yielding a corrected significance level of
P < .007 (0.05/7). We computed Cohen d effect sizes using postestimation margins (effect sizes of 0.2, 0.5 and 0.8 represent
small, medium, and large effects, respectively69).
To explore the effect of age on the association between psychotic experiences and neuropsychological functioning, local
regression curves for age on the interaction of cognition by
group were plotted for each test. To test the effect of age formally, we entered an interaction of group (psychotic experiences vs control) by age (continuous) with centered variables68
into the regression model, adjusting for confounders as above.
Linear regression analyses were subsequently stratified by age
group (16-24, 25-34, 35-49, and ≥50 years), adjusting for confounders as above. Age categories were selected based on lo132
Ten participants with missing PSQ data, 8 participants reporting a current or a past diagnosis of psychosis, and 3 participants currently taking antipsychotics were excluded from the
analyses. The remaining 1677 participants were ethnically diverse (633 [37.7%] not white British), with a mean (SD) age of 40
(17) years (range, 16-90 years). Seven hundred thirty-three participants were male (43.7%).
Based on self-report and medication use, 11 participants
(prevalence, 0.7%) had psychotic illness, which is consistent
with previous reports of prevalence.1,2 The 1-year weighted
prevalence of psychotic experiences, defined as positive responses to all secondary questions in 1 or more categories on
the PSQ,5 included 171 participants (9.7%), which is consistent with findings from the World Health Survey.72
The group with psychotic experiences was more likely to
be of a minority ethnic background, have a lower occupational status, have used cannabis in the past year, and have a
common mental disorder (eTable 4 in the Supplement). Age
differences in prevalence were not statistically significant.
Association of Psychotic Experiences
With Neuropsychological Deficits
Table 2 shows the relationship between psychotic experiences and neuropsychological performance before and after
adjusting for confounders. The IQ impairment did not reach
statistical significance when adjusting for confounders
(β = −3.78; t1261 = −1.91; P = .06; Cohen d = −0.22). However,
significant impairments were seen in the WTAR (β = −4.21;
t1347 = −3.02; P = .003; Cohen d = −0.37), SDRT (β = −1.15;
t1385 = −2.84; P = .005; Cohen d = −0.34), VOLT (β = −1.94;
t1455 = −2.59; P = .01; Cohen d = −0.28), and VOLT delay (β
= −0.66; t1411 = −2.37; P = .02; Cohen d = −0.24) scores. Impairments in the WTAR and SDRT scores remained statistically significant after correcting for multiple comparisons. No
statistically significant impairment in the DSCT score was seen
before or after adjusting for confounders.
We performed an exploratory analysis of the association
between each psychotic experience (thought insertion, paranoia, strange experiences, and hallucinations) and neuropsychological performance. All experiences were associated with
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Psychotic Experiences and Neuropsychological Functioning
Original Investigation Research
Table 2. Group Means and Effect Sizes Before and After Adjustments
Mean (SD) Score by Group
Cognitive Test
Psychotic Experiences
Control
Effect Size,
Cohen da
P Valueb
Effect Size,
Cohen dc
IQd
95.25 (16.58)
100.45 (14.77)
−0.37
<.001
−0.22
.06
WTAR totale
31.36 (15.78)
38.83 (12.64)
−0.58
<.001
−0.37
.003
P Valueb
SDRTf
Total
20.97 (4.12)
22.51 (3.26)
−0.46
<.001
−0.34
.005
Low load
11.32 (2.40)
12.02 (1.92)
−0.36
<.001
−0.27
.02
9.66 (2.13)
10.49 (1.85)
−0.45
<.001
−0.33
.004
VOLTg
High load
43.80 (8.45)
46.53 (7.06)
−0.38
<.001
−0.28
.01
VOLT delayh
14.27 (2.97)
15.14 (2.75)
−0.31
<.001
−0.24
.02
DSCTi
40.63 (13.06)
42.17 (13.79)
−0.12
.20
−0.03
.73
Abbreviations: DSCT, digit symbol coding task; SDRT, Spatial Delayed-Response
Task; VOLT, Visual Object Learning Task; WTAR, Wechsler Test of Adult Reading.
e
Scores range from 0 to 50, with higher scores indicating better performance.
f
Scores range from 0 to 24, with higher scores indicating better performance.
a
Indicates unadjusted.
g
Scores range from 0 to 60, with higher scores indicating better performance.
b
Results are statistically significant at the Bonferroni corrected level of P < .007.
h
Scores range from 0 to 20, with higher scores indicating better performance.
c
Indicates adjusted for ethnicity and occupational class, cannabis use in last
year, and common mental disorders.
i
Scores range from 0 to 94, with higher scores indicating better performance.
d
Scores range from 40 to 160, with higher scores indicating better
performance.
cognitive impairment, but effect sizes varied (eTable 5 in the
Supplement). The frequency of individual symptoms did not
allow stratification by age.
(eFigure 2 in the Supplement). Adjusting additionally for educational level (eTable 6 and eFigure 3 in the Supplement) also
produced similar results.
Association Between Neuropsychological Functioning
and Psychotic Experiences Stratified by Age
Association Between Neuropsychological Functioning
and Psychotic Experiences by Familial Factors
Previous studies have used samples consisting mostly of children and adolescents or of older adults, but inspection of Table 1
suggests that the association between psychotic experiences
and neuropsychological functioning may differ by age. Figure 1
shows an overall age-associated cognitive decline in both
groups but also a difference in the severity of neuropsychological impairment associated with psychotic experiences at
different ages. We found significant group-by-age interactions for all neuropsychological measures, including IQ
(P = .006), WTAR (P = .01), SDRT (P = .03), VOLT (P = .001),
VOLT delay (P = .02), and DSCT (P = .01) scores when adjusting for confounders.
After stratifying by age group and adjusting for confounders, group differences in mean (SD) IQ (81.22 [15.97] vs 91.28
[14.31]; Cohen d = −0.70), WTAR (28.31 [13.83] vs 38.51 [11.50];
Cohen d = −0.88), SDRT (19.11 [4.77] vs 21.99 [3.42]; Cohen
d = −0.82), VOLT (39.17 [8.23] vs 44.09 [6.51]; Cohen d = −0.45),
and VOLT delay (13.09 [2.74] vs 14.34 [2.40]; Cohen d = −0.52)
scores were medium to large in participants with psychotic experiences 50 years and older (Figure 2). Medium impairments in SDRT (21.27 [3.64] vs 22.62 [2.97]; Cohen d = −0.45)
and VOLT (44.32 [5.84] vs 46.91 [5.74]; Cohen d = −0.45) scores
were also found in participants aged 35 to 49 years with psychotic experiences and a medium impairment (30.81 [14.17]
vs 37.60 [10.48]; Cohen d = −0.62) and a medium advantage
(44.80 [6.61] vs 38.63 [8.43]; Cohen d = 0.74) in WTAR scores
in those aged 16 to 24 and 25 to 34 years, respectively. All other
impairments in those younger than 50 years were small.
Sensitivity analysis using a different cutoff for the presence of psychotic experiences70,71 produced similar results
Characteristics of each group are shown in eTable 7 in the
Supplement. Exploratory analyses (eFigure 4 in the Supplement) suggested that WTAR performance was the most and
VOLT performance was the least familial. First-degree relatives of probands were impaired on the WTAR score (β = −3.93;
t1347 = −2.33; P = .02; Cohen d = −0.36) after adjusting for confounders (Figure 3). Nongenetically related cohabitants did not
show statistically significant neuropsychological deficits.
jamapsychiatry.com
Discussion
This study provides evidence that subclinical psychotic experiences are associated with mild neuropsychological impairment in adults. The magnitude of impairment in specific domains suggests impaired verbal and memory functions but
spared processing speed. Only older adults with psychotic experiences showed medium to large impairments in working
memory and memory when adjusting for sociodemographic
factors, psychiatric morbidity, and cannabis use. First-degree
relatives of probands also had a significant verbal impairment, but not a significant memory impairment. Our findings
introduce new knowledge and propose new hypotheses regarding the neuropsychology of psychotic experiences in adults.
Our results are in line with those of the National Survey
of Psychiatric Morbidity in Great Britain,5 which reported a
small verbal IQ deficit in adults reporting psychotic experiences. Although not directly comparable to those from other
previous studies, which have mostly focused on younger or
older samples,19,20,23,24 the adjusted effect sizes we report
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Research Original Investigation
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Figure 1. Local Regression Curves of Neuropsychological Functioning Domains
A Wechsler test of adult reading
B
Control group
Psychotic experiences group
24
Total No. of Correct Responses
Total No. of Correct Responses
50
Spatial delayed response task
40
30
20
22
20
18
16
10
20
40
60
80
100
20
40
60
Age, y
C
100
80
100
D Digit symbol coding task
Visual object learning task
50
No. of Correct Responses in 90 s
60
Total No. of Correct Responses
80
Age, y
50
40
30
20
40
30
20
20
40
60
80
100
20
40
60
Age, y
Age, y
Domains are designated by the neuropsychological test used. Interaction of age by group is depicted on the graphs. The Wechsler Test of Adult Reading assessed verbal
knowledge; the Spatial Delayed Response Task, working memory; the Visual Object Learning Task, visual memory; and the digit symbol coding task, processing speed.
Figure 2. Effect Sizes for Each Neuropsychological Domain by Age Group
A Before adjustment
IQ
1.5
B
After adjustment
IQ
1.5
WTAR
WTAR
SDRT
SDRT
VOLT
1.0
VOLT
1.0
DSCT
0.5
0
−0.5
−1.0
−1.5
VOLT delay
Effect Size, Cohen d
Effect Size, Cohen d
VOLT delay
DSCT
0.5
0
−0.5
−1.0
16-24
25-34
35-49
≥50
−1.5
16-24
25-34
Age Group, y
35-49
≥50
Age Group, y
Data are depicted before and after adjusting for confounders. The Wechsler Test of Adult Reading (WTAR) assessed verbal knowledge; the Spatial Delayed Response Task
(SDRT), working memory; the Visual Object Learning Task (VOLT), visual memory; and the digit symbol coding task (DSCT), processing speed. Error bars indicate 95% CIs.
closely approximate the pooled effect sizes in our metaanalytic summary (Table 1). Adjustment for confounders attenuated the processing speed deficit, suggesting that the sig134
nificant processing speed deficits reported in children and
adolescents with psychotic experiences19,20 may be partly confounded. Alternatively, the cause of processing speed defi-
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Psychotic Experiences and Neuropsychological Functioning
jamapsychiatry.com
Figure 3. Effect Sizes for Each Neuropsychological Domain
by Familial Group
0.4
0.2
Effect Size, Cohen d
cits associated with psychotic experiences may differ between adolescence and adulthood. Indeed, a recent study that
used a dimensional categorization of psychotic experiences also
did not find differences in processing speed between adults
with low and high levels of psychotic experiences.73
Our findings highlight similarities, but also differences, between neuropsychological dysfunction associated with psychotic experiences vs disorders. Meta-analyses have shown the
most severe cognitive impairment in schizophrenia to be in processing speed.44,45 We found only a weak association between psychotic experiences and DSCT performance. The discrepancy between a substantial processing speed impairment
in psychotic disorder and a negligible impairment in psychotic experiences suggests that clinical psychosis is associated with increasing abnormality in processing speed.74 Our
findings add to a growing body of literature that challenges psychotic experiences as a subclinical phenotype of psychosis.
Identification of factors associated with psychotic experiences that predict transition to psychotic disorder is needed
if they are to be useful in the etiologic investigation of psychosis. Neuropsychological impairment, in processing speed
specifically, may be one factor. Individuals with psychotic experiences and processing speed deficits may be most at risk
for psychosis, and this combination of risk factors warrants further longitudinal study.
This study was the first, to our knowledge, to investigate
the effect of age on neuropsychological impairment associated with psychotic experiences in adults. Some studies suggest that these experiences are most prevalent in adolescence75
and old age,76 whereas meta-analyses have not found significant age differences.3,47,48 In our sample, prevalence of psychotic experiences was greatest in the youngest group but remained sizable in the other age groups (eTable 4 in the
Supplement). Only older adults showed medium to large deficits in IQ, verbal knowledge, working memory, and memory
after adjustment for multiple demographic and psychosocial
factors. Medium impairments in working memory and memory
were seen in the group aged 35 to 49 years and in verbal knowledge in the group aged 16 to 24 years. These findings highlight
the heterogeneity of extended phenotypic expression associated with psychotic experiences throughout adulthood. Etiopathologic pathways to subclinical psychotic experiences and
neuropsychological dysfunction may be age dependent (eFigure 5 in the Supplement). In young adults with psychotic experiences, neuropsychological impairment may signal a risk for
general psychiatric disorders, possibly owing to psychosocial
stress and/or substance use; however, in older adults, neuropsychological impairment may indicate vulnerability to accelerated cognitive aging. A faster trajectory of cognitive decline
for patients with Alzheimer disease with concurrent delusions77
and hallucinations78 has been reported. Accelerated shrinkage of prefrontal and hippocampal regions seen in normal
aging79,80 may lead to disrupted dopamine release and psychotic phenomena81 but also to more rapid cognitive decline.
By including cohabitants of participants with psychotic
experiences, we explored potential mechanisms behind the
association between psychotic experiences and cognition.
First-degree relatives were significantly impaired on verbal
Original Investigation Research
0
−0.2
−0.4
−0.6
−0.8
IQ
VOLT
WTAR
VOLT delay
SDRT
DSCT
−1.0
Unrelated Cohabitant
First-Degree Relative
Proband With Psychotic
Experiences
Familial Group
Effect sizes are adjusted for all confounders. The Wechsler Test of Adult Reading
(WTAR) assessed verbal knowledge; the Spatial Delayed Response Task (SDRT),
working memory; the Visual Object Learning Task (VOLT), visual memory; and the
digit symbol coding task (DSCT), processing speed. Error bars indicate 95% CIs.
knowledge, whereas unrelated cohabitants showed no
impairment. Our findings suggest that a complex interplay
of genetic, biological, and psychosocial factors lies behind
the association between psychotic experiences and neuropsychological impairment. This pattern of verbal knowledge
impairment suggests common genetic and/or family environmental factors. On the other hand, unimpaired memory
functions in both groups of cohabitants support biological
and/or psychosocial effects of psychotic experiences on
memory consistent with a causal effect.
Although we hypothesize that sociodemographic factors, cannabis use, and common mental disorders are confounders, they could also be mediators or moderators. Mediation and confounding are identical statistically but can be
distinguished conceptually.82 Changes associated with the hypothalamic-pituitary-adrenal axis may be one area of investigation because the hypothalamic-pituitary-adrenal axis has
been associated with all of these factors and with psychosis
and cognition.83 Shared genetic factors could be another area
of investigation.84,85 Examining interactions between multiple risk factors is important because complex multifactorial
traits are likely to result from such interactions, and future studies with large samples are required for such investigations.86
The present study has a number of strengths. It is the first,
to our knowledge, to use a large, heterogeneous, representative sample drawn from an urban community to investigate
the effect of age and familial factors on the association between psychotic experiences and neuropsychological functioning while adjusting for important confounders. Nevertheless, several methodologic limitations require consideration.
First, the 51.9% household participation rate was high, but we
were not able to characterize nonresponders on demographic variables and rule out possible bias owing to nonparticipation. However, the sample was representative of the local population on most sociodemographic characteristics.50,71
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135
Research Original Investigation
Psychotic Experiences and Neuropsychological Functioning
Second, psychotic experiences are fairly common in old age,
presumably owing to neurodegenerative processes,87 and we
could not exclude participants with dementia. However, most
of the participants in the oldest category were aged 50 to 65
years, when dementia is rare,88 and medium to large impairments in IQ, WTAR, SDRT, and VOLT scores (Cohen d > 0.50
for all) remained when we excluded participants older than 65
years. Third, interpretation of effect sizes generally depends
on the assumption of normality, which held true for all tasks
except the WTAR, meaning that effect sizes in verbal knowledge may have been underestimated.
Moreover, those participants with poorer neuropsychological functioning may have been more likely to endorse psychotic experiences, and yet the association was not present at
all ages or in all domains. We cannot infer from the current
cross-sectional data that psychotic experiences lead to deficits in neuropsychological functioning. Another plausible explanation is that psychotic experiences and neuropsychologi-
ARTICLE INFORMATION
Submitted for Publication: June 25, 2015; final
revision received October 14, 2015; accepted
October 20, 2015.
Published Online: December 30, 2015.
doi:10.1001/jamapsychiatry.2015.2551.
Author Affiliations: Department of Psychosis
Studies, Institute of Psychiatry, Psychology, and
Neuroscience, King’s College London, London,
England (Mollon, David, Pilecka, Reichenberg);
Department of Health Services and Population
Research, Institute of Psychiatry, Psychology, and
Neuroscience, King’s College London, London,
England (Morgan); Department of Psychological
Medicine, Institute of Psychiatry, Psychology, and
Neuroscience, King’s College London, London,
England (Frissa, Hatch, Hotopf); Department of
Psychiatry, Yale University, New Haven,
Connecticut (Glahn); Department of Psychiatry,
Icahn School of Medicine at Mount Sinai, New York,
New York (Reichenberg); Department of Preventive
Medicine, Icahn School of Medicine at Mount Sinai,
New York, New York (Reichenberg); Friedman Brain
Institute, Icahn School of Medicine at Mount Sinai,
New York, New York (Reichenberg).
Author Contributions: Ms Mollon had full access to
all the data in the study and takes responsibility for
the integrity of the data and the accuracy of the
data analysis.
Study concept and design: David, Morgan, Glahn,
Hatch, Hotopf, Reichenberg.
Acquisition, analysis, or interpretation of data:
Mollon, David, Morgan, Frissa, Pilecka, Hatch,
Hotopf, Reichenberg.
Drafting of the manuscript: Mollon, David,
Reichenberg.
Critical revision of the manuscript for important
intellectual content: All authors.
Statistical analysis: Mollon, Glahn, Pilecka,
Reichenberg.
Obtained funding: David, Hatch, Hotopf.
Administrative, technical, or material support:
David, Morgan, Frissa, Glahn, Hatch, Hotopf.
Study supervision: David, Morgan, Reichenberg.
Conflict of Interest Disclosures: None reported.
Funding/Support: This study was supported by the
Biomedical Research Nucleus data management
136
cal functioning are manifestations of common underlying
processes.89,90 Finally, the timing and history of psychotic experiences cannot be established from the PSQ, meaning that
some psychotic experiences may be long-standing. The present data provide valuable insight into potential pathways to
adult psychopathologic disorders, but future longitudinal studies that are able to disentangle their temporal sequence and
to determine whether these findings also apply to lifetime psychotic experiences are needed.
Conclusions
The profile of cognitive impairment in adults with psychotic
experiences differed from that found in psychotic disorders.
Our findings highlight the importance of considering age, familial factors, and the psychosocial context in neuropsychological studies of psychotic experiences.
and informatics facility at South London and the
Maudsley NHS (National Health Service)
Foundation Trust, which is funded by the National
Institute for Health Research (NIHR) Mental Health
Biomedical Research Centre at South London,
Maudsley NHS Foundation Trust, King’s College
London, and a joint infrastructure grant from Guy’s
and St Thomas’ Charity and the Maudsley Charity.
Ms Mollon is supported by the Medical Research
Council. Drs Frissa, Hatch, and Hotopf receive
salary support from the NIHR Mental Health
Biomedical Research Centre at South London,
Maudsley NHS Foundation Trust, and King’s College
London.
Role of the Funder/Sponsor: The funding sources
had no role in the design and conduct of the study;
collection, management, analysis, and
interpretation of the data; preparation, review, or
approval of the manuscript; and decision to submit
the manuscript for publication.
Disclaimer: The views expressed herein are those
of the authors and not necessarily those of the
NHS, the NIHR, or the Department of Health.
Additional Contributions: We thank all the study
participants. The following additional members of
the SELCoH (South East London Community
Health) study team assisted: project coordinator
Maria Verdecchia, MSc, and project manager Aysha
Begum, DClinPsych (both of Department of
Psychological Medicine, Institute of Psychiatry,
Psychology, and Neuroscience, King’s College
London, London, England); coinvestigators Robert
Stewart, PhD (Department of Psychological
Medicine, Institute of Psychiatry, Psychology, and
Neuroscience, King’s College London), and Nicola T.
Fear, PhD (King’s Centre for Military Health
Research, King’s College London); and research
assistants Bwalya Kankulu, MSc, Jennifer Clark,
PhD, Billy Gazard, MSc, Robert Medcalf, DClinPsych,
Alistair Baile, BSc, Elizabeth Doherty, BSc, Deborah
Bekele, MSc, Joshua Buckman, DClinPsych, Grant
Henderson, BSc (all of Department of Psychological
Medicine, Institute of Psychiatry, Psychology, and
Neuroscience, King’s College London), Helena
Brundy, BSc (Department of Psychosis Studies,
Institute of Psychiatry, Psychology, and
Neuroscience, King’s College London), and
Benedict Weobong, PhD (Kintampo Health
Research Centre, Ghana Health Service, Kintampo,
Brong Ahafo Region, Ghana). The research
assistants were paid to collect data. No other
compensation was given.
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